Pralidoxime reactivates acetylcholinesterase (AChE) that has been deactivated by binding of organophosphates to its esteratic site.1 Pralidoxime binds to the anionic site of AChE and displaces the phosphate from the esteratic site through formation of phosphate-pralidoxime conjugates. It reactivates paraoxon- and diisopropyl fluorophosphate-inactivated human red blood cell (RBC) AChE with IC50 shifts of 0.3 and 0.8 nM per μM of pralidoxime, respectively.2,3 At a concentration of 10 μM, it reactivates human RBC AChE that has been inactivated by chlorpyrifos , diazinon , and malathion by 17, 61, and 36%, respectively.4 Pralidoxime binds to sarin-bound hAChE (Kd = 25.72 μM) and inhibits sarin-induced AChE deactivation (IC50 = 1.21 mM) in hemoglobin-free erythrocyte ghosts.5 Formulations containing pralidoxime have been used to treat organophosphate poisoning.1
1.Jokanovi?, M., and Stojiljkovi?, M.P.Current understanding of the application of pyridinium oximes as cholinesterase reactivators in treatment of organophosphate poisoningEur. J. Pharmacol.553(1-3)10-17(2006) 2.Petroianu, G.A., Arafat, K., Kuca, K., et al.Five oximes (K-27, K-33, K-48, BI-6 and methoxime) in comparison with pralidoxime: In vitro reactivation of red blood cell acetylcholinesterase inhibited by paraoxonJ. Appl. Toxicol.26(1)64-71(2006) 3.Lorke, D.E., Hasan, M.Y., Arafat, K., et al.In vitro oxime protection of human red blood cell acetylcholinesterase inhibited by diisopropyl-fluorophosphateJ. Appl. Toxicol.28(4)422-429(2008) 4.Costa, M.D., Freitas, M.L., Soares, F.A., et al.Potential of two new oximes in reactivate human acetylcholinesterase and butyrylcholinesterase inhibited by organophosphate compounds: An in vitro studyToxicol. In Vitro25(8)2120-2123(2011) 5.Karade, H.N., Raviraju, G., Acharya, B.N., et al.Synthesis and in vitro reactivation study of isonicotinamide derivatives of 2-(hydroxyimino)-N-(pyridin-3-yl)acetamide as reactivators of Sarin and VX inhibited human acetylcholinesterase (hAChE)Bioorg. Med. Chem.24(18)4171-4176(2016)